After a particle accelerator causes a freak storm, CSI Investigator Barry Allen is struck by lightning and falls into a coma. Months later he awakens with the power of super speed, granting him the ability to move through Central City like an unseen guardian angel. Though initially excited by his newfound powers, Barry is shocked to discover he is not the only "meta-human" who was created in the wake of the accelerator explosion -- and not everyone is using their new powers for good. Barry partners with S.T.A.R. Labs and dedicates his life to protect the innocent. For now, only a few close friends and associates know that Barry is literally the fastest man alive, but it won't be long before the world learns what Barry Allen has become...The Flash.

Barry is living his dream life – his parents are alive, he’s asked Iris West on a date and he can finally be a normal guy as Central City has another speedster, Kid Flash, running around saving the city. When Barry starts forgetting parts of his old life, the Reverse Flash taunts his nemesis and tells him that there will be serious repercussions for Barry and the ones he loves if he continues to live in this alternate universe. In addition to losing his memories, his powers will also start to fade. When disaster strikes, Barry must decide if he wants to continue to live in this world as Barry Allen or return to his universe as The Flash.

Barry and Team Flash are thrilled to reunite with Earth-2 Wells and Jesse. Wells confides to Barry and Caitlin that Jesse has all the powers of a speedster and has been saving people on his Earth. He is concerned about her safety and wants them to talk her out of using her powers. Meanwhile, Magenta, a new meta who can control metal, terrorizes the city.

Barry continues to train Jesse and when a new meta human, Mirror Master, appears on the scene he lets her tag along. Mirror Master has teamed up with his old partner, Top, and is looking for Snart to even a score. Jesse is quick to join the chase but defies one of Barry’s orders which results in disastrous consequences.

Caitlin goes to her mother to help understand the meta-human powers growing inside her. Meanwhile Barry tries to convince Julian to allow him to help investigate a new human meta-attack on Central City.

Caitlin uses her powers to save Barry but as her mother predicted, the effort unleashes her inner Killer Frost. Killer Frost goes on a rampage looking for Dr. Alchemy, kidnapping Julian and battling both The Flash and Vibe. Meanwhile, Joe and H.R. have a heart to heart talk.

When aliens called the Dominators attack Central City, Barry speeds over to Star City to ask the Green Arrow for help in stopping them. Realizing the battle against the Dominators is bigger than they thought, they track down the Legends of Tomorrow, and Barry and Cisco create a breach to bring back a secret weapon – Supergirl. Once all of the super friends are assembled, they come up with a plan to attack but a shocking secret related to Flashpoint is revealed and suddenly no one is sure who they can trust. Meanwhile, Wally wants to join the battle against the aliens but Iris tells him he’s not ready.
The crossover starts on Supergirl S02E08 Medusa (I). It continues on Arrow S05E08 Invasion! (III) and DC's Legends of Tomorrow S02E07 Invasion! (IV).

With Alchemy and Savitar still looming threats, Barry is unable to focus on the Christmas holiday, and especially his relationship with Iris. Determined to stop Savitar, Barry goes to Earth-3 to get advice from Jay Garrick. Wally wants to help Barry fight Savitar and reveals that he’s been training with H.R, which doesn’t go over well with Barry. As Cisco faces his first Christmas without his brother Dante, old wounds are reopened.

Barry is tormented by his vision of the future where Iris is murdered by Savitar. When a criminal named Plunder shows up in Central City, Barry recalls the villain’s presence in his vision of the future and fears that if he catches Plunder, it will cement Iris’ fate. Confused about Barry’s hesitation to stop Plunder, Wally decides to step in as Kid Flash. Caitlin offers Julian a job.

H.R.'s past catches up with him when a bounty hunter with vibe powers named Gypsy arrives in Central City to bring him back to Earth-19 to stand trial for his crime. It turns out inter-dimensional travel is illegal on their Earth. H.R. surrenders but when Barry and Cisco find out that H.R.’s only hope would be to challenge Gypsy to a fight to the death, they intercede and Cisco offers to fight Gypsy instead.

Barry and the team at S.T.A.R. Labs work together to bring down Clive Yorkin, a criminal meta-human who is methodically killing people by causing them to decompose at an accelerated rate. Joe becomes his next target but it’s Iris who is caught in the crossfire. The Flash mentors Kid Flash and begins to elevate the newer speedster’s training to another level.

When Jesse Quick informs the team that her father has been abducted, Barry, Caitlin, Cisco and Julian voyage to Earth-2 on a rescue mission to save Harry from Gorilla City. As they trek through the forest, Barry and the team are immediately captured and brought to Grodd. Grodd tells them he needs their help to stop Solovar, the leader of Gorilla City, as Solovar wants to invade Earth-1. Meanwhile, back on Earth-1, Jesse and Kid Flash hit the streets to stop a metahuman that can control gravity, with H.R. and Joe guiding them from S.T.A.R. Labs.

When Grodd and his army of gorillas bring the battle to Earth-1, The Flash and team must find a way to stop them before they destroy Central City. Gypsy returns to join the fight. Meanwhile, Jesse Quick decides she wants to stay with Wally on Earth-1.

Barry and team are surprised when Mon-El and Hank Henshaw arrive on their Earth carrying a comatose Supergirl who was whammied by the Music Meister. Unable to wake her up, they turn to Team Flash to save her. However, the Music Meister surprises The Flash and puts him in a similar coma, one that Team Flash can’t cure. Kara and Barry wake up without their powers in an alternate reality where life is like a musical and the only way to escape is by following the script, complete with singing and dancing, to the end.

Barry travels to the future to find out Savitar’s still unknown identity in the hopes of saving Iris. Upon his arrival in 2024, Barry encounters future versions of his Team Flash friends, who, following the death of Iris, have become very different people, profoundly impacted by their showdown with Savitar. It will be up to Barry to infuse a sense of hope back into the team, as he proves to be hero his future friends have been waiting for. Meanwhile, back in 2017, the hunt for Killer Frost continues.

Barry and the team meet Tracy Brand, a scientist, who may be the key to stopping Savitar. Unfortunately, Killer Frost is also after Tracy so Team Flash must battle their old friend, which proves to be particularly difficult for Cisco. Joe and Cecile’s relationship takes a big turn.

With only 24 hours left until Savitar murders Iris, Barry struggles to save the woman he loves and makes the choice to use any means necessary to do so. Realizing he has one option left to save her, The Flash turns to Captain Cold for help.